Effect of CagriSema, Semaglutide and Cagrilintide on Insulin Sensitivity and Pancreatic Endocrine Function in Adults With Type 2 Diabetes
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- To compare the effect of CagriSema versus placebo: Change in M-value in hyperinsulinaemic euglycaemic clamp (HEC)
研究概览
简要总结
This study will look at how CagriSema, semaglutide and cagrilintide regulate insulin effects in the body of people with type 2 diabetes (T2D). CagriSema is a new investigational medicine that combines two medicines called cagrilintide and semaglutide. Doctors may not yet prescribe CagriSema. Participants will either get CagriSema, semaglutide, cagrilintide, or a ''dummy'' medicine. Which treatment the participants will get is decided by chance. Participants will get the study medicine together with the current daily diabetes medicine metformin. Participants should not take other medicines for diabetes during the study. The study will last for about 42 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female.
- •Aged 18-75 years (both inclusive) at the time of signing informed consent.
- •Diagnosed with type 2 diabetes greater than or equal to (>=) 180 days before screening.
- •Stable daily dose(s) of metformin at effective or maximum tolerated dose, as judged by the investigator for 90 or more days before screening with or without one additional oral antidiabetic drug (OAD), except for the use of glucagon-like peptide-1 (GLP-1) receptor agonists, or sodium-glucose co-transporter-2 (SGLT-2) inhibitors in case of a high risk of cardiovascular disease (as judged by the investigator), or established cardiovascular disease, or chronic kidney disease (Glomerular Filtration Rate (eGFR) less than (<) 60 milliliter per minute per 1.73 square meter [ml/min/1.73 m^2]).
- •Glycated hemoglobin (HbA1c) at screening of 6.5-9.5 percent (48-80 millimoles per mole [mmol/mol]) (both inclusive) if on metformin only, or 6.0- 9.0 percent (42-75 mmol/mol) (both inclusive) if on metformin in combination with one other OAD. A minimum of 65% of randomised participants must have HbA1c >= 7.0 % at screening.
- •Body Mass index (BMI) between 25.0 and 45.0 kilogram per square meter (kg/m^2) (both inclusive) at screening.
排除标准
- •Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method.
- •Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- •Renal impairment with estimated Glomerular Filtration Rate (eGFR) < 45 ml/min/1.73 m^2 at screening.
- •Treatment with any medication for the indication of T2D or weight management other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed.
研究组 & 干预措施
CagriSema
Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Semaglutide (Drug)
CagriSema
Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Cagrilintide (Drug)
CagriSema
Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Placebo semaglutide (Drug)
CagriSema
Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Placebo cagrilintide (Drug)
Semaglutide
Participants will receive once-weekly s.c injections of semaglutide at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Semaglutide (Drug)
Semaglutide
Participants will receive once-weekly s.c injections of semaglutide at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Placebo semaglutide (Drug)
Cagrilintide
Participants will receive once-weekly s.c injections of cagrilintide at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Cagrilintide (Drug)
Cagrilintide
Participants will receive once-weekly s.c injections of cagrilintide at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks.
干预措施: Placebo cagrilintide (Drug)
Placebo
Participants will receive once-weekly s.c injection of placebo matched to semaglutide and cagrilintide for 28 weeks.
干预措施: Placebo semaglutide (Drug)
Placebo
Participants will receive once-weekly s.c injection of placebo matched to semaglutide and cagrilintide for 28 weeks.
干预措施: Placebo cagrilintide (Drug)
结局指标
主要结局
To compare the effect of CagriSema versus placebo: Change in M-value in hyperinsulinaemic euglycaemic clamp (HEC)
时间窗: Baseline to week 28
M-value from the HEC is calculated from glucose infusion rate (GIR) over the last 30 minutes of the clamp, corresponding to steady state. M-value is defined as: (GIR150-180 min normalised by body weight \[milligram per minute per kilogram {mg/min/kg}\]). Measured in mg/min/kg.
次要结局
- To compare the effect of CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC(Baseline to week 28)
- To compare the effect of CagriSema versus placebo, CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC, normalised by lean body mass(Baseline to week 28)
- Change in total insulin response (total AUC0-120 min) in HGC(Baseline to week 28)
- Change in clamp disposition index (cDI) calculated from HEC and HGC(Baseline to week 28)
- Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose)(Baseline to week 28)
- Change in glucose concentration during MMTT (total and incremental AUC0-300min)(Baseline to week 28)
- Change in cDI calculated from HEC and HGC,based on lean body mass(Baseline to week 28)
- Change in β-cell glucose sensitivity (insulin secretion) from HGC(Baseline to week 28)
- Change in insulin concentration during MMTT (total and incremental AUC0-300min)(Baseline to week 28)
- Change in C-peptide concentration during MMTT (total and incremental AUC0-300min)(Baseline to week 28)
- Change in glucagon concentration during MMTT (total and incremental AUC0-300min)(Baseline to week 28)
- Change in fasting glucose concentration (MMTT pre-meal concentrations)(Baseline to week 28)
- Change in fasting insulin concentration (MMTT pre-meal concentrations)(Baseline to week 28)
- Change in fasting C-peptide concentration (MMTT pre-meal concentrations)(Baseline to week 28)
- Change in fasting glucagon concentration (MMTT pre-meal concentrations)(Baseline to week 28)
- Change in fasting proinsulin concentration (MMTT pre-meal concentrations)(Baseline to week 28)
- Change in HbA1c(Baseline to week 28)
- Change in systolic and diastolic blood pressure(Baseline to week 28)
- Number of Treatment Emergent Adverse Events (TEAEs)(Baseline to end of study (week 34))
- Change in first-phase incremental insulin secretion rate (ISR0-8min) in hyperglycaemic clamp (HGC)(Baseline to week 28)
- Change in total insulin secretion rate (ISR0-120min) in HGC(Baseline to week 28)
- Change in second-phase insulin secretion rate (ISR20-120min) in HGC(Baseline to week 28)
- Change in insulin secretion rate at fixed glucose concentration (ISRg) in HGC(Baseline to week 28)
- Change in insulin response to arginine (incremental insulin AUCarginine,0-10min) in HGC(Baseline to week 28)
- Change in C-peptide response to arginine (incremental insulin AUCarginine,0-10min) in HGC(Baseline to week 28)